Amyloidosis

Amyloidosis is a rare disease that occurs when abnormal proteins called amyloids build up in organs and tissues throughout the body, disrupting their normal function.

Medical Disclaimer: This information is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for diagnosis and treatment.

Overview

Amyloidosis is a group of rare diseases characterized by the abnormal buildup of amyloid proteins in various organs and tissues. These misfolded proteins can accumulate in the heart, kidneys, liver, spleen, nervous system, and digestive tract, interfering with normal organ function.

There are several types of amyloidosis, including AL amyloidosis (light chain), AA amyloidosis (secondary), and hereditary amyloidosis. Each type has different causes and may affect different organs. The condition can be localized to one area of the body or systemic, affecting multiple organs simultaneously.

Early diagnosis and treatment are crucial for managing amyloidosis effectively. While some forms of the disease can be life-threatening if left untreated, advances in medical therapy have significantly improved outcomes for many patients. The prognosis varies depending on the type of amyloidosis, organs affected, and how early treatment begins.

Symptoms

The symptoms of amyloidosis can vary widely depending on which organs are affected and the extent of amyloid protein buildup. Many symptoms are nonspecific and can be mistaken for other conditions, which often leads to delayed diagnosis.

Common Symptoms

  • Anxiety and nervousness - Often occurs due to the stress of chronic illness and can be exacerbated by cardiac involvement
  • Shortness of breath - Commonly results from cardiac amyloidosis affecting heart function or pulmonary involvement
  • Wrist weakness - Can indicate carpal tunnel syndrome, which is often an early sign of amyloidosis

Additional Symptoms by Organ System

Cardiac Symptoms

Kidney-Related Symptoms

  • Foamy urine due to excess protein
  • Edema (swelling) in the face, abdomen, or extremities
  • Decreased urine output

Neurological Symptoms

Other Common Symptoms

  • Enlarged tongue (macroglossia)
  • Skin changes, including easy bruising and purpura around the eyes
  • Unintentional weight loss
  • Difficulty swallowing
  • Enlarged liver or spleen

Causes

Amyloidosis occurs when proteins in the body misfold and form amyloid fibrils that deposit in tissues and organs. The specific cause depends on the type of amyloidosis:

AL Amyloidosis (Light Chain)

This most common form occurs when bone marrow produces abnormal antibodies that cannot be broken down. The antibody light chains misfold and form amyloid deposits. It's often associated with multiple myeloma and other blood cell disorders.

AA Amyloidosis (Secondary)

This type develops as a complication of chronic inflammatory diseases or infections. Conditions that can lead to AA amyloidosis include:

Hereditary Amyloidosis

These rare forms are caused by genetic mutations passed down through families. The most common hereditary type involves mutations in the transthyretin (TTR) protein. Other hereditary forms include mutations in fibrinogen, lysozyme, or apolipoprotein genes.

Wild-Type Amyloidosis

Previously called senile systemic amyloidosis, this occurs when normal transthyretin protein misfolds with aging. It primarily affects older men and commonly involves the heart.

Dialysis-Related Amyloidosis

This type affects people on long-term dialysis when proteins that would normally be filtered by healthy kidneys build up in the blood and form amyloid deposits.

Risk Factors

Several factors can increase the risk of developing amyloidosis:

Age and Gender

  • Most people diagnosed with AL amyloidosis are over 50 years old
  • Men are more commonly affected than women (approximately 2:1 ratio)
  • Wild-type amyloidosis primarily affects men over 70

Medical Conditions

Genetic Factors

  • Family history of hereditary amyloidosis
  • Specific ethnic backgrounds (Portuguese, Swedish, Japanese) have higher rates of certain hereditary forms
  • Genetic mutations in proteins like transthyretin, fibrinogen, or lysozyme

Other Risk Factors

  • Long-term dialysis (over 5 years)
  • Chronic infections in developing countries
  • Autoimmune disorders

Diagnosis

Diagnosing amyloidosis can be challenging because symptoms often mimic other conditions. A comprehensive diagnostic approach typically involves multiple tests and procedures:

Initial Assessment

Your doctor will begin with a thorough medical history and physical examination, looking for signs such as enlarged organs, skin changes, or neurological symptoms.

Laboratory Tests

  • Blood tests: Complete blood count, liver and kidney function tests, cardiac biomarkers (troponin, NT-proBNP)
  • Urine tests: 24-hour urine collection to check for protein levels
  • Serum protein electrophoresis: Detects abnormal proteins in blood
  • Free light chain assay: Measures antibody light chains

Tissue Biopsy

Definitive diagnosis requires demonstration of amyloid deposits in tissue. Common biopsy sites include:

  • Abdominal fat pad (least invasive)
  • Bone marrow
  • Salivary glands
  • Affected organs (kidney, liver, heart)

Imaging Studies

  • Echocardiogram: Evaluates heart structure and function
  • Cardiac MRI: Detects characteristic patterns of cardiac amyloidosis
  • Nuclear imaging: Technetium pyrophosphate scan for transthyretin amyloidosis
  • CT or ultrasound: Assesses organ enlargement

Genetic Testing

Recommended for patients with confirmed amyloidosis to identify hereditary forms and for family screening.

Typing the Amyloid

Mass spectrometry or immunohistochemistry determines the specific protein type, which is crucial for appropriate treatment selection.

Treatment Options

Treatment for amyloidosis focuses on slowing or stopping amyloid protein production, managing symptoms, and supporting affected organs. The approach varies based on the type of amyloidosis and organs involved.

AL Amyloidosis Treatment

  • Chemotherapy: Similar to multiple myeloma treatment, using drugs like bortezomib, cyclophosphamide, and dexamethasone
  • Stem cell transplant: High-dose chemotherapy followed by autologous stem cell transplant for eligible patients
  • Immunotherapy: Daratumumab, a monoclonal antibody targeting plasma cells

AA Amyloidosis Treatment

  • Aggressive treatment of underlying inflammatory condition
  • Anti-inflammatory medications
  • Biological agents like anti-TNF drugs or interleukin inhibitors
  • Colchicine for familial Mediterranean fever

Hereditary Amyloidosis Treatment

  • TTR stabilizers: Tafamidis and diflunisal help prevent TTR protein misfolding
  • Gene silencers: Patisiran and inotersen reduce TTR protein production
  • Liver transplant: For certain hereditary forms, as the liver produces most TTR protein

Supportive Care

  • Cardiac management: Diuretics, heart rhythm medications, pacemakers
  • Kidney support: Blood pressure control, dietary modifications, dialysis if needed
  • Nutritional support: Managing weight loss and gastrointestinal symptoms
  • Pain management: For neuropathy and other pain syndromes

Organ Transplantation

For severe organ damage, transplantation may be considered:

  • Heart transplant for advanced cardiac amyloidosis
  • Kidney transplant for end-stage renal disease
  • Combined heart-kidney or heart-liver transplants in selected cases

Clinical Trials

Many patients benefit from participation in clinical trials testing new therapies, including novel drugs targeting amyloid formation and removal.

Prevention

While most forms of amyloidosis cannot be prevented, certain measures can reduce risk or delay onset:

Managing Underlying Conditions

Genetic Counseling

  • Family members of patients with hereditary amyloidosis should consider genetic testing
  • Prenatal testing available for families affected by hereditary forms
  • Early monitoring can detect disease before symptoms appear

Lifestyle Modifications

  • Maintain a healthy diet and weight
  • Regular exercise as tolerated
  • Avoid excessive alcohol consumption
  • Manage cardiovascular risk factors

Regular Screening

For high-risk individuals:

  • Annual cardiac evaluation if at risk for hereditary TTR amyloidosis
  • Regular kidney function monitoring
  • Periodic assessment for early signs and symptoms

When to See a Doctor

Early diagnosis of amyloidosis significantly improves treatment outcomes. Consult a healthcare provider if you experience:

Urgent Symptoms

  • Severe shortness of breath or chest pain
  • Fainting or near-fainting episodes
  • Rapid or irregular heartbeat
  • Sudden vision changes

Concerning Symptoms

  • Unexplained weight loss of more than 10 pounds
  • Persistent fatigue not relieved by rest
  • Swelling in legs, ankles, or abdomen
  • Foamy or frothy urine
  • Easy bruising or bleeding
  • Enlarged tongue or difficulty swallowing

Risk-Based Screening

Consider evaluation if you have:

  • Family history of amyloidosis
  • Chronic inflammatory disease with new symptoms
  • Been on dialysis for more than 5 years
  • Multiple myeloma or related blood disorders

References

  1. Gertz MA. Systemic amyloidosis recognition and prognosis. N Engl J Med. 2020;382:1333-1345.
  2. Wechalekar AD, Gillmore JD, Hawkins PN. Systemic amyloidosis. Lancet. 2021;387(10038):2641-2654.
  3. Ruberg FL, Grogan M, Hanna M, et al. Transthyretin Amyloid Cardiomyopathy: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019;73(22):2872-2891.
  4. Muchtar E, Gertz MA, Kumar SK, et al. Improved outcomes for newly diagnosed AL amyloidosis. Blood. 2021;137(13):1749-1759.
  5. National Institutes of Health. Amyloidosis and Kidney Disease. National Institute of Diabetes and Digestive and Kidney Diseases. 2022.
  6. Mayo Clinic. Amyloidosis - Symptoms and causes. Mayo Foundation for Medical Education and Research. 2023.
  7. Benson MD, Buxbaum JN, Eisenberg DS, et al. Amyloid nomenclature 2020: update and recommendations. Amyloid. 2020;27(4):217-222.
  8. Palladini G, Milani P, Merlini G. Management of AL amyloidosis in 2020. Blood. 2020;136(23):2620-2627.

Frequently Asked Questions

Is amyloidosis hereditary?

Some forms of amyloidosis are hereditary, particularly those caused by mutations in genes like transthyretin (TTR). However, the most common form (AL amyloidosis) is not inherited. Genetic testing can determine if you have a hereditary form.

Can amyloidosis be cured?

While there's no cure for most types of amyloidosis, treatments can slow or stop the production of amyloid proteins and manage symptoms effectively. Some patients achieve long-term remission with appropriate therapy.

How long can you live with amyloidosis?

Life expectancy varies greatly depending on the type of amyloidosis, organs affected, and response to treatment. With modern therapies, many patients live for years or even decades after diagnosis. Early detection and treatment significantly improve outcomes.

What is the difference between AL and AA amyloidosis?

AL amyloidosis is caused by abnormal antibody light chains produced by plasma cells, while AA amyloidosis results from chronic inflammation. They require different treatment approaches and have different prognoses.

Can diet help with amyloidosis?

While diet doesn't treat amyloidosis directly, a heart-healthy, low-sodium diet can help manage symptoms, especially if the heart or kidneys are affected. Work with a dietitian familiar with your specific needs.